title: Prevention of EGF-modulated adhesion of tumor cells to matrix proteins by specific EGF receptor inhibition.
abstract: The adhesion of tumor cells to various extracellular matrix (ECM) proteins is influenced by epidermal growth factor (EGF). Maximal effects are obtained at low EGF concentrations, at which mostly the cytoskeleton-associated high-affinity EGF receptors (EGFRs) are saturated. Tumor cells expressing EGFR either endogenously (MDA MB 231, MTLn3) or, for the human EGFR, ectopically (MTC HER1/1) in intermediate amounts exhibited, upon EGF addition, increased cellular adhesion to various ECM proteins, such as fibronectin, collagens and vitronectin. In contrast, human A431 and MDA MB 468 cells, over-expressing EGFR, demonstrated reduced attachment in similar experimental conditions. Both increased as well as reduced EGF-dependent adhesion could be blocked using either ligand-blocking monoclonal antibody 14E1 or the potent EGFR tyrosine kinase inhibitor PD 153035. Our data indicate that signals downstream of EGFR activation are responsible for the opposing effects of EGF on cellular adhesion since both can be prevented by EGFR inhibition. Thus, the integration of EGFR- and integrin-dependent signals can be different in carcinoma cell lines and might be influenced by EGFR numbers.
authors.affiliation: Research Laboratories of Schering AG, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Genersch
authors.forename: D W
authors.initials: DW
authors.lastname: Schneider
authors.forename: G
authors.initials: G
authors.lastname: Sauer
authors.forename: K
authors.initials: K
authors.lastname: Khazaie
authors.forename: D
authors.initials: D
authors.lastname: Schuppan
authors.forename: R B
authors.initials: RB
authors.lastname: Lichtner
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D016326:Extracellular Matrix Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors